Neurology

Scientists grow mini 'human brain' in the lab

Much of the media is reporting the news that researchers have for the first time used stem cells to create a "mini-brain" – tiny clumps of highly complex neural tissue that could provide new insights into brain development.

Researchers found that when grown in a laboratory, the stem cells were able to self-assemble into structures resembling developing brain regions, and that these structures were able to interact.

These "mini-brain" regions, termed "organoids" by the researchers, were tiny – less than 4mm across. While this may not initially sound impressive, many commentators have described brain tissue as "the most complex object in the known universe".

For those worried that this may be the first step towards a lab-grown thinking machine, this is not what the researchers wanted to achieve. It is unclear whether this would ever be possible or, perhaps more importantly, ethical. What the researchers in fact set out to do is create a kind of model of the human brain at its very early stages.

This could offer a novel approach for studying diseases that originate during the very early stages of brain development. It could also avoid some of the difficulties that arise in applying animal research to humans because of the physical differences between humans and animals.

Overall, this is an exciting development in the field of neurological research, but it is in very early stages and it is unclear precisely what the implications are.

Where did the story come from?

The study was carried out by researchers from the Austrian Academy of Sciences, the University of Edinburgh, the Wellcome Trust Sanger Institute and St George's University, London, and was funded by the Medical Research Council, the European Research Council, the Wellcome Trust and other research grant organisations.

The study was published in the peer-reviewed journal Nature.

This research was covered well by the media, with most outlets focusing on the ground-breaking nature of the study while also addressing its limitations.

Refreshingly, the media resisted the temptation to sensationalise the implications of the study with wild claims of Frankenstein-like mad doctors trying to create a living, thinking being. All the sources made clear that this was not the researchers' intention.

What kind of research was this?

This was a laboratory study involving the use of stem cells to build a model of the human brain.

What did the research involve?

Stem cells are cells that have not yet developed into specialised cells with specific functions, such as nerve cells, blood cells or muscle. The researchers took human stem cells, derived from either embryonic stem cells or adult skin, and supplied them with nutrients and oxygen to support their development into brain tissue and structures. They then examined the form and organisation of these tissues and their similarity to human brain regions and structures.

In an early attempt, the researchers used the new approach to model a condition called microcephaly. Microcephaly is an uncommon neurological disorder in which the brain only grows to an abnormally small size. Previous studies into the mechanics of the disease using mice have not been particularly useful.

To do this, the researchers recruited a person with microcephaly and derived induced pluripotent stem cells (iPS) from their skin. They then used these cells to model brain development.

What were the basic results?

The study's authors report that the stem cells were able to self-organise into small organs the researchers termed "cerebral organoids" that represent separate but interdependent brain regions. They were able to identify tissues similar to several developing brain structures, including the:

  • cerebral cortex – the outer layer of the brain, sometimes called grey matter, which plays an important role in higher brain functioning
  • choroid plexus – a structure ultimately responsible for the production of cerebrospinal fluid, the fluid that surrounds and supports the brain
  • retina – the light-sensitive tissue at the back of the eyes
  • meninges – the membranes that surround the brain and spinal cord

The researchers also found that the organoids displayed key features of human brain development. These features included patterns of cell organisation expected to be seen during the early stages of development. While the regions seemed to interact, the arrangement varied across the different tissue samples and no consistent overall structure was seen.

The tissues grew for approximately two months, with the organoids reaching a maximum size of approximately 4mm in diameter. Although growth stopped, the tissue continued to survive up to 10 months (when the study ended). The researchers think that the lack of continuous growth is likely because of the lack of a circulatory system, which limits the ability to supply oxygen-rich blood and nutrients to the developing tissues.

When the researchers examined tissue development in the microcephaly model, they found that the developed tissues were smaller than those from control cells and the stem cells differentiated into neural cells earlier than control cells. 

How did the researchers interpret the results?

The researchers concluded that this study represents "a novel approach for studying human neurodevelopmental processes" – that is, how the human brain develops.

They feel it could provide a useful model for studying these processes and could ultimately uncover some of the "roots of human neurological disease".

Conclusion

This exciting research represents the first time researchers have been able to grow complex interconnected brain-like structures in a lab.

While scientists and neurological disorder experts are quite excited about the development, it is still early and the implications of the study are largely unknown at this stage. However, the ability to model microcephaly neural development provides an early example of the potential applications of this approach.

The researchers suggest that their results show that this technique may be a useful way of studying neurological disorders and the developmental stage of brain development.

This is especially useful for conditions that we do not have appropriate animal models for because of the differences in brain development between animals and humans. As many media outlets reported, these conditions may include autistic spectrum disorder and schizophrenia.

Overall, this study represents a novel and exciting advancement in neurology. Whether it ultimately changes how we study and understand brain development and the processes that cause neurological disorders remains to be seen.


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